Mannose-binding lectin plays a critical role in myocardial ischaemia and reperfusion injury in a mouse model of diabetes

Aims/hypothesis Diabetic patients are at increased risk of cardiomyopathy, acute myocardial infarction and loss of cardiac progenitor cells (CPCs), but the aetiology is poorly understood. We hypothesised a significant role for mannose-binding lectin (MBL) in cardiomyopathies associated with hyperglycaemia. Methods The role of MBL in myocardial ischaemia and reperfusion (MI/R) injury was investigated in wild-type (WT) and MBL-null mice following 2 weeks of streptozotocin-induced hyperglycaemia. Results Hyperglycaemic WT mice presented with significantly decreased left ventricular ejection fractions and increased serum troponin I levels and myocardial inflammation compared with non-diabetic WT mice following MI/R. Hyperglycaemic MBL-null mice or insulin-treated diabetic WT mice were significantly protected from MI/R injury compared with diabetic WT mice. In an additional study using diabetic WT mice, echocardiographic measurements demonstrated signs of dilative cardiomyopathy, whereas heart:body weight ratios suggested hypertrophic cardiac remodelling after 2 weeks of hyperglycaemia. Immunohistochemical analysis of CPCs showed significantly lower numbers in diabetic WT hearts compared with non-diabetic hearts. Insulin-treated diabetic WT or untreated diabetic MBL-null mice were protected from dilative cardiomyopathy, hypertrophic remodelling and loss of CPCs. Conclusions/interpretation These data demonstrate that MBL may play a critical role in diabetic MI/R injury. Further, the absence of MBL appears to inhibit hypertrophic remodelling and hyperglycaemia-induced loss of CPCs after just 2 weeks of hyperglycaemia in mice.